The University of Queensland, Delivery of Drugs and Genes Group, Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD 4072, Australia.
J Control Release. 2012 Apr 30;159(2):215-21. doi: 10.1016/j.jconrel.2012.01.030. Epub 2012 Jan 28.
Many vaccines make use of an adjuvant to achieve stronger immune responses. Alternatively, potent immune responses have also been generated by replacing the standard needle and syringe (which places vaccine into muscle) with devices that deliver vaccine antigen to the skin's abundant immune cell population. However it is not known if the co-delivery of antigen plus adjuvant directly to thousands of skin immune cells generates a synergistic improvement of immune responses. In this paper, we investigate this idea, by testing if Nanopatch delivery of vaccine - both the antigen and the adjuvant - enhances immunogenicity, compared to intramuscular injection. As a test-case, we selected a commercial influenza vaccine as the antigen (Fluvax 2008®) and the saponin Quil-A as the adjuvant. We found, after vaccinating mice, that anti-influenza IgG antibody and haemagglutinin inhibition assay titre response induced by the Nanopatch (with delivered dose of 6.5ng of vaccine and 1.4μg of Quil-A) were equivalent to that of the conventional intramuscular injection using needle and syringe (6000ng of vaccine injected without adjuvant). Furthermore, a similar level of antigen dose sparing (up to 900 fold) - with equivalent haemagglutinin inhibition assay titre responses - was also achieved by delivering both antigen and adjuvant (1.4μg of Quil-A) to skin (using Nanopatches) instead of muscle (intramuscular injection). Collectively, the unprecedented 900 fold antigen dose sparing demonstrates the synergistic improvement to vaccines by co-delivery of both antigen and adjuvant directly to skin immune cells. Successfully extending these findings to humans with a practical delivery device - like the Nanopatch - could have a huge impact on improving vaccines.
许多疫苗利用佐剂来实现更强的免疫反应。或者，通过用将疫苗抗原递送至皮肤丰富的免疫细胞群的装置替代标准的针和注射器（将疫苗递送至肌肉），也产生了有效的免疫反应。然而，尚不清楚抗原加佐剂的共同递送至数千个皮肤免疫细胞是否会产生免疫反应的协同改善。在本文中，我们通过测试纳米贴剂（既传递抗原又传递佐剂）是否比肌肉内注射更能增强免疫原性来研究这个想法。作为一个测试案例，我们选择了一种商业流感疫苗作为抗原（Fluvax 2008®）和皂苷 Quil-A 作为佐剂。我们发现，在给小鼠接种疫苗后，纳米贴剂（传递 6.5ng 疫苗和 1.4μg Quil-A）诱导的抗流感 IgG 抗体和血凝抑制试验滴度与传统的使用针和注射器的肌肉内注射（6000ng 未加佐剂的疫苗）相当。此外，通过将抗原和佐剂（1.4μg Quil-A）递送至皮肤（使用纳米贴剂）而不是肌肉（肌肉内注射），也实现了类似水平的抗原剂量节省（高达 900 倍），同时保持血凝抑制试验滴度相当。总的来说，前所未有的 900 倍抗原剂量节省证明了通过将抗原和佐剂共同直接递送至皮肤免疫细胞，对疫苗的协同改善。成功地将这些发现扩展到具有实用递送装置（如纳米贴剂）的人类身上，可能会对改善疫苗产生巨大影响。
